P450 enzyme induction assay

Enzyme induction assays are generally performed for the evaluation of the effects of the substance tested on P450 induction. For animal studies, liver enlargement (e.g. liver weight gain) as well as increases in P450 activities after a relevant treatment period (e.g. 14 days) are used as endpoints for enzyme induction potential. 

Table 4 Drug metabolizing enzyme (P450 isoforms (CYP), UDP-glucuronosyl transferase (UGT) and phenol sulfotransferase (PST)) substrates that can be used for the in situ measurement of activity in the human hepatocyte enzyme induction assay.

Metabolism and drug-drug interaction issues are discovered by screening for inhibition and induction of cytochrome P450 liver enzymes (CYP450). FDA guidelines have specific recommendation for substrates (Table 7.2) and inhibitors (Table 7.3) to be nsed in these assays. 

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